the overallgoals of our project remain unchanged from our original application: to carry out a program of research to develop non-invasive assessment tools, grounded in known physiological mechanisms, in infants at risk for SIDS and other developmental disorders. To continue this mission we have expanded our approach and our multidisciplinary team of perinatal researchers in order to develop new risk indices as early as possible In the life of the fetus and young infant. Over the next Ave years we will be assessing approximately 80 infants/year In the Northern Plains and 100 subjects/year in NYC from the late fetal through the early newborn period. In these studies we propose to incorporate more direct measures of CNS maturation during sleep, as well as more sophisticated analyses of autonomic nervous system regulation in both the fetus and infant in healthy and at-risk populations. Our physiological studies focus on testing both healthy term and at-risk, prematurely born infants in response to physiological challenges associated with changes in sleep state, prone vs supine sleep positions, and orthostatic tilt. These studies are conducted prior to and during the age range of greatest vulnerability for SIDS. In addition to our battery of existing measurements of respiration, heart rate, blood pressure, movement, EEG and temperature, we propose to incorporate new state of the art measures of venous return and tissue perfusion, as we believe these parameters will provide more direct information about the physiological forces that drive responses to alterations in tilt and sleep position. In addition, we will expand our use of fetal ECG monitoring to more comprehensively assess autonomic and cardiac function in the late term fetus. Specifically, with the Monica abdominal fECG device we will investigate maternal/fetal ECG interactions, the effect of uterine activity on fetal heart rate, incidence and variation in fetal arrhythmias, fetal movement and heart rate coupling, patterns of heart rate variability and fetal heart rate response to sound. This new technology will also allow access to markers of perinatal autonomic function in both time and frequency domains, previously only accessible in the infant. We also propose to augment our autonomic challenges to include investigation of arousal and learning. We have found an important cortical component to tilt and a strong relationship of cortical power and synchrony with postconceptlonal age and later outcome. We have also developed analytic toots that can quantify arousal, i.e., cortical activation, in response to sensory stimulation and while learning during Sleep. We propose to extend our investigations of cortical and cerebellar markers of reactivity and learning during sleep In both healthy and high risk premature infants prior to discharge from the hospital and at one month of age. We predict that altered patterns of electrocortical synchrony will be associated with adverse prenatal exposures, both in premature infants and in the high risk sample from the Northern Plains. In these populations we will continue to measure local and distal coherence, as well as high frequency spectral power, parameters we have shown to be altered during tilts and which are affected by sleep positions. The additional EEG measures will provide more comprehensive estimates of individual physiological trajectories following adverse exposures. Consistent with our initial proposal we will export new comprehensive assessment techniques developed in our Columbia laboratories to assess a vulnerable population (Native Americans in the Northern Plains). This work, which in past years was conducted on the Pine Ridge Indian Reservation in South Dakota, was curtailed due to budget cuts in our last application. However, we now plan to merge our efforts with those of another NICHD/NIAAA study being conducted by the PASS netwok in Rapid City, S.D' In these studies, we will measure EEG and autonomic activity as a function of prenatal risk factors in one month old Infants during sleep in both prone and supine positions and in response to a tilt challenge. In summary, our primary hypotheses focus on testing how known risk factors for SIDS (postnatal age, premature birth, sleep position, prenatal exposures) alter physiological function in the fetus and infant. Our long-term objectives are to elucidate physiologic mechanisms that underlie SIDS and to develop age-appropriate, non-invasive tests that will identify infants who are at the greatest risk. These primary hypotheses and goals remain as stated in our original application.